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Biomedical subjects

M R Freeman

Publications and source records attributed to M R Freeman.

At least 91 records · Page 5Linked to original sources
PubMed1991

Ultrastructural studies of unstable angina in living man.

Nineteen patients with refractory unstable angina who were undergoing aortocoronary bypass were studied to assess the extent of platelet aggregation present in the microvasculature. Ultrastructural findings on the morphology of cardiac muscle and microvasculature were correlated with the findings on coronary angiograms and thallium scans. There were no significant correlations. The presence of platelet aggregates was identified in four biopsies, two of which had thrombus by angiographic criteria. Biopsy in areas with thallium defects revealed an increased prevalence of white blood cells without acute myocardial infarction. This study confirms the presence of platelet aggregates in patients with unstable angina, albeit at a reduced frequency when compared with autopsy studies.

Aged↗
PubMed1990

Prognosis in medically stabilized unstable angina: early Holter ST-segment monitoring compared with predischarge exercise thallium tomography.

OBJECTIVE: To assess the relative value of invasive and noninvasive predictors of outcome in patients after unstable angina. DESIGN: Cohort of 54 patients with unstable angina who had 6-month follow-up after stabilization on medical therapy. SETTING: University-based hospital, tertiary referral center. PATIENTS: Consecutive patients with unstable angina whose symptoms resolved while receiving medical therapy. MEASUREMENTS AND MAIN RESULTS: We prospectively compared 24-hour Holter ST-segment monitoring at admission, quantitative exercise thallium tomography, and cardiac catheterization 5 +/- 2 days after admission and analyzed their value for predicting a cardiac event in patients with unstable angina within 6 months. When patients with a favorable outcome (n = 40) were compared with patients with an unfavorable outcome (n = 11) no statistical difference was found in duration of ST shift of 1 mm or more on Holter monitoring (51 +/- 119 min compared with 37 +/- 43 min), exercise duration by the standard Bruce protocol (8.0 +/- 3.6 min compared with 7.9 +/- 3.1 min), exercise-induced ST depression (0.6 +/- 0.9 mm compared with 1.0 +/- 1.0 mm), and contrast left ventricular ejection fraction (70% +/- 10% compared with 69% +/- 15%). Patients with a favorable outcome were distinguished from those with an unfavorable outcome by a higher maximum rate-pressure product (24 x 10(3) +/- 6 x 10(3) compared with 18 x 10(3) +/- 7 x 10(3), P = 0.0025), smaller size of the reversible scintigraphic perfusion defect expressed as a percentage of total myocardium imaged (6% +/- 11% compared with 17% +/- 18%, P = 0.05) and a smaller number of vessels with stenosis of 50% or more (1.1 +/- 1.2 compared with 2.1 +/- 1.0, P = 0.01). On multiple logistic regression analysis, a history of previous myocardial infarction was the most powerful predictor of outcome. In patients without myocardial infarction, reversible exercise thallium perfusion defect size was the only predictor. CONCLUSION: After stabilization of an episode of unstable angina, quantitative tomographic exercise thallium scintigraphy has greater value for risk stratification than Holter ST-segment monitoring, particularly in patients who have not had a previous infarction.

Adult↗
PubMed1990

Fibroblast-mediated acceleration of human epithelial tumor growth in vivo.

Transformed fibroblasts coinoculated with epithelial cells accelerated the growth and shortened the latency period of human epithelial tumors in athymic mice. Addition of NbF-1 fibroblasts caused epithelial tumors to grow from five marginally tumorigenic or "nontumorigenic" (nontumor-forming) human tumor cell lines or strains: PC-3 (prostate), WH (bladder), MDA-436 (breast), and cells derived from the ascites fluids of patients with metastatic renal pelvic or prostate cancers. Evidence for the human and epithelial nature of these experimental tumors was provided by histologic, immunohistochemical, Southern and dot-blot hybridization, and cytogenetic analyses. Transformed fibroblasts induced predominantly carcinosarcomas, whereas nontumorigenic fibroblasts (NIH 3T3) and lethally irradiated transformed fibroblasts induced exclusively carcinomas. The fibroblast-epithelial interaction appears to occur bidirectionally and does not result from cell fusion. Because coculture experiments in vitro did not demonstrate an increased cell proliferation, it appears that undefined host factors can influence tumor growth. This tumor model may be useful in drug-screening programs and in mechanistic studies of factors regulating human tumor growth and progression.

Animals↗
PubMed1990

Regulation of gene expression in rat prostate by androgen and beta-adrenergic receptor pathways.

Denervation of rat ventral prostate has been accomplished by excising prostatic tissue fragments and implanting them under the renal capsules of intact syngeneic rats. This resulted in a substantial reduction of expression of a major organ-specific secretory protein, prostatic binding protein (PBP). The depressed level of PBP and its subunits and mRNAs could be restored, however, to as much as 80% of control levels by the administration of a pharmacological dose of exogenous androgen, testosterone propionate (TP), and/or a beta-adrenergic agonist, isoproterenol (ISO). Furthermore, compared to ascorbate-treated controls, TP and ISO increased the synthesis of total cellular protein and PBP by the prostatic renal implants. TP and/or ISO also remodelled the luminal epithelial structure and elevated secretory functions. ISO alone had no effect, however, in castrated animals, indicating that androgen plays a dominant role in the restoration of tissue PBP content. Concomitant to increased PBP content and remodelling of prostatic histomorphology, androgen was also found to raise the depressed levels of beta 2-adrenergic and androgen receptors in the prostatic isografts maintained in intact hosts. In contrast, although an established rat prostatic epithelial cell line (NbE-1) contains high affinity androgen receptor, androgen failed to restore beta-adrenergic receptor as well as PBP content in this cultured cell line. These results, taken together, suggest that a tight coupling between androgen receptor and beta 2-adrenergic receptor pathways may be a prerequisite for PBP expression and functional differentiation in the rat ventral prostate gland.

Androgen-Binding Protein↗
PubMed1989

Aberrant expression of epidermal growth factor receptor and HER-2 (erbB-2) messenger RNAs in human renal cancers.

Amplification, rearrangement, or overexpression of the gene for the epidermal growth factor receptor (EGFR) occurs in certain types of human neoplasia. We investigated EGFR gene structure and measured EGFR mRNA levels in human renal tumor biopsies. Seventeen renal tumors [13 renal cell carcinomas (RCCs), two Wilms' tumors, one oncocytoma, and one metastatic ganglioneuroblastoma] and their corresponding normal kidney tissues were examined for EGFR gene structural integrity by Southern blot hybridization. Twelve of these tumors (including 11 RCCs) were examined for EGFR mRNA expression levels by RNA blot hybridization. The EGFR gene was rearranged in one of 13 (8%) of the RCC specimens examined and was highly amplified in the ganglioneuroblastoma. The overall frequency of EGFR gene structure alterations in this series of renal tumors was 12%. Nine of 11 RCC specimens (82%) exhibited markedly elevated EGFR mRNA levels (approximately 2- to 6-fold). In contrast, expression of the EGFR-related protooncogene HER-2 (erbB-2) was found to be decreased in 11 RCCs and one Wilms' tumor; HER-2 gene structure, however, appeared normal in all specimens. These results indicate that overexpression of EGFR mRNA, probably due to changes in gene regulation, and underexpression of HER-2 mRNA are characteristic features of human RCC.

Actins↗
PubMed1989

Changes in jugular venous flow velocity after coronary artery bypass grafting.

The factors underlying postoperative jugular venous flow velocity and pulse contour changes were studied in 25 patients undergoing coronary artery bypass grafting. Before operation, all patients had normal right-sided cardiac hemodynamics, normal jugular pulse contours and normal jugular venous flow velocity patterns, i.e., systolic flow (SF) velocity greater than diastolic flow (DF) velocity. After operation, jugular venous flow velocity was abnormal in 24 patients (SF = DF in 14 and SF less than DF in 10). Neither the right-sided cardiac pressures after the operation nor any of the perioperative factors examined had any bearing on these flow alterations. Postoperative right ventricular ejection fraction was normal in all 5 patients with SF greater than DF and SF = DF flow patterns (mean +/- standard error of the mean 48 +/- 3%). It was significantly depressed in all 6 patients with SF less than DF flow pattern (34 +/- 1%, 2p less than 0.001). These findings suggest that the right atrium behaves as a conduit rather than a capacitance chamber. However, the postoperative abnormal flow pattern of SF less than DF as opposed to SF = DF indicates the additional presence of right ventricular dysfunction. The implications of these observations for the clinical assessment of right ventricular function in the postoperative patients are discussed.

Adult↗
PubMed1989

Role of resting thallium201 perfusion in predicting coronary anatomy, left ventricular wall motion, and hospital outcome in unstable angina pectoris.

We performed quantitative thallium scintigraphy in 66 unstable angina patients, 5.6 +/- 5.1 hours after rest pain, to predict coronary anatomy, left ventricular wall motion, and hospital outcome. Thallium defects and/or washout abnormalities were present in 5 of 10 (50%) patients with coronary stenoses less than 50%, 27 of 33 (82%) patients with coronary stenosis greater than or equal to 50% and no history of previous myocardial infarction, and in 23 of 23 patients (100%) with histories of previous infarction. Defects were uncommon in the territory of vessels with less than 50% (13 of 61, 21%), but significantly more common in the territory of vessels with greater than or equal to 50% stenosis (57 of 137, 42%), p less than 0.005. With the addition of washout abnormalities to defect analysis, sensitivity for detection of coronary stenoses improved to 67% (92 of 137), p less than or equal to 0.005, but specificity fell to 59% (36 of 61), p less than 0.01. Segmental wall motion abnormalities were less common in segments with normal perfusion (21%) or in those with washout abnormalities alone (19%), than in segments with thallium defects (45%, p less than 0.005). Defects in patients with previous infarction were common in both segments, with normal (26 of 66, 40%) or abnormal (24 of 45, 53%) wall motion. Eleven of 18 patients with in-hospital cardiac events, but no history of myocardial infarction, had resting thallium defects, whereas only 8 of 25 patients without cardiac event had thallium defect (p = 0.056).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Regulation of the S100 protein and GFAP genes is mediated by two common mechanisms in RT4 neuro-glial cell lines.

RT4-AC cells express both neuronal and glial properties and undergo cell-type conversion in culture to three distinct derivatives, described as either neuronal-like or glial-like. A coordinate induction of glial fibrillary acidic protein (GFAP) and S100 protein and GFAP gene expression is coordinately induced by cAMP. In addition, for the first time we provide direct evidence that the ability to express both the S100 and GFAP genes is conserved with cell-type conversion to the glial derivative cell types, but is coordinately lost with conversion to the neuronal derivative cell types. These results make it highly likely that the GFAP and S100 genes are regulated by two common mechanisms in RT4-AC cells: (1) cAMP-mediated control of gene expression; and (2) a mechanism that allows these two genes to be coordinately expressed or not expressed as a consequence of cell-type conversion.

Animals↗
PubMed1989

Tissue plasminogen activator: Toronto (TPAT) placebo-controlled randomized trial in acute myocardial infarction.

The efficacy and safety of recombinant tissue plasminogen activator (rt-PA) administered on a dosing per weight basis was evaluated in a randomized, placebo-controlled, double-blind trial in 115 patients with acute myocardial infarction. The principal outcomes were global and regional left ventricular function in the distribution of the qualifying myocardial infarction, determined 9 days after the onset of symptoms. Global and regional ejection fraction values were significantly better for patients treated with rt-PA than for placebo-treated patients (the differences were 5.8 +/- 2.7% units [p = 0.017] and 7.1 +/- 3.1% units [p = 0.012], respectively). This benefit was also evident from visual assessment of left ventricular segmental wall motion. After adjustment for differences in important prognostic variables at baseline, the estimates of treatment effect were 4.0 +/- 2.4% units (p = 0.048) for global and 4.3 +/- 2.6% units (p = 0.047) for regional ejection fraction. Early patency of the infarct-related vessel was demonstrable in 7 (29%) of 24 placebo-treated patients and 18 (78%) of 23 rt-PA-treated patients, whereas 15 (56%) of 27 patients in the placebo group and 23 (72%) of 32 in the rt-PA group had a patent infarct-related vessel at hospital day 9. There was no significant difference in irreversible or reversible defect size as assessed by thallium scintigraphy on day 7.(ABSTRACT TRUNCATED AT 250 WORDS)

Double-Blind Method↗
PubMed1989

ST segment shift in unstable angina: pathophysiology and association with coronary anatomy and hospital outcome.

The significance of ST segment shift with respect to coronary anatomy and hospital outcome was evaluated in 135 patients with unstable angina. ST shift was evident in 44% of patients on admission electrocardiogram (ECG) and in 66% on Holter monitor ECG. During hospitalization, 7% of patients had myocardial infarction, 4% died and 34% had urgent coronary revascularization. By comparing patients with and without ST shift on admission ECG, an unfavorable outcome was found in 55% versus 25% (p less than 0.005), multivessel disease in 77% versus 63% (p less than 0.05) and left main coronary artery stenosis in 22% versus 7% (p less than 0.025). When patients with and without ST shift on Holter monitor ECG were compared, an unfavorable outcome was found in 48% versus 20% (p less than 0.005), multivessel disease in 76% versus 54% (p less than 0.01) and left main coronary stenosis in 18% versus 4% (p less than 0.05). The duration of ST shift was also greater in patients with 1) unfavorable outcome (129 +/- 136 versus 52 +/- 111 min, p less than 0.01); 2) multivessel disease (98 +/- 129 versus 36 +/- 90 min, p less than 0.01); and 3) left main stenosis (150 +/- 147 versus 67 +/- 114 min, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1989

New etiology for intestinal uptake of thallium-201.

A patient with both rest and exercise thallium images for unstable angina demonstrated marked large intestinal uptake of thallium. However, the thallium uptake in the large intestine was noted only after exercise. The only change in the patient status between the two studies was the administration of verapamil. Thus, verapamil administration has been demonstrated to be a new cause for gut uptake of thallium.

Angina, Unstable↗
PubMed1989

Intracoronary thrombus and complex morphology in unstable angina. Relation to timing of angiography and in-hospital cardiac events.

In 78 consecutive patients with unstable angina, we performed coronary angiography randomized to either the first day of presentation or later during the hospital admission to assess the frequency of intracoronary thrombus and complex coronary morphology relative to the time of symptomatic presentation and the impact of these angiographic features on outcome. Early angiography (17 +/- 6 hours) was performed in 42 patients and late angiography in 36 patients (5.7 +/- 2.1 days). Twelve patients randomized to late angiography required urgent cardiac catheterization 3.9 +/- 2.2 days after admission. Coronary thrombi were present in 43% (18 of 42) of early angiography patients and in 38% (14 of 36) of late angiography patients (p = NS). Only 21% (five of 24) late elective angiography patients had coronary thrombi, but 75% (nine of 12) of late urgent angiography patients had thrombi (p less than 0.05 vs. both early and late elective angiography patients). There was no difference in the frequency of complex coronary morphology among patients randomized to early angiography (42%, or 15 of 36), late urgent angiography (42%, or five of 12), and late elective angiography (38%, or nine of 24). Cardiac events (death, myocardial infarction, and urgent revascularization) were more frequent in the patients with coronary thrombus (73%, or 23 of 32), complex coronary morphology (55%, or 16 of 29), and multiple-vessel disease (58%, or 29 of 50) than in the patients without these angiographic features (17%, or eight of 46; 31%, or 15 of 49; and 7%, or two of 28, respectively; all p less than 0.05). Multiple regression analysis demonstrated that coronary thrombus was the best angiographic predictor of cardiac events. Thus, angiographic detection of intracoronary thrombi varies according to the temporal relation between angiography and chest pain at rest.

Angina Pectoris↗
PubMed1989

Comparison of rest and exercise thallium-201 kinetics in man and implications for quantitation.

To develop a technique for quantitative analysis of resting thallium scintigrams, an understanding of thallium kinetics at rest is required. This study evaluates in normal man the thallium distribution and washout rates of thallium at rest and compares these findings to similar data obtained during exercise. The thallium half-life in normal resting myocardium is significantly longer than after exercise, 10.2 +/- 1.4 hours versus 3.9 +/- 0.3 hours (P less than .01). Differences in resting thallium half-life exist between the anterior, 45 degrees left anterior oblique (LAO), and 70 degrees LAO views and are 11.4 +/- 1.0, 10.6 +/- 1.0, 8.8 +/- 0.7 hours, respectively (all significantly different from each other by ANOVA, P less than or equal to .01); these differences are related to the imaging sequence. After exercise, the thallium half-life also varies according to imaging sequence, but in the opposite direction; i.e., anterior, 45 degrees LAO, and 70 degrees LAO views are 3.6 +/- 0.1, 3.9 +/- 0.3, 4.2 +/- 0.3 hours, respectively (P less than or equal to .01). Since imaging sequence and time of acquisition at rest and exercise were similar, this finding may be related to earlier maximal uptake of thallium after exercise as compared to rest. There are also significant segmental differences in thallium half-life at rest in the 45 degrees LAO view (9.8 +/- 0.9, septal vs. 11.0 +/- 0.9, posterolateral, P less than .01) and 70 degrees LAO view (8.3 +/- 0.4, anteroseptal vs. 9.2 +/- 0.6, inferior, P less than or equal to .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Usefulness of exercise electrocardiography and thallium scintigraphy in unstable angina pectoris in predicting the extent and severity of coronary artery disease.

The safety and efficacy of exercise electrocardiography and thallium scintigraphy early in the course of unstable angina pectoris were assessed 4.6 +/- 1.6 days after admission in 67 patients with unstable angina that stabilized after medical therapy. Coronary arteriography was performed in all patients 5.4 +/- 2.4 days after admission. There was no difference in clinical, exercise or scintigraphic variables between patients with stenoses less than 50% and patients with 1-vessel coronary artery disease (CAD) defined as a diameter stenosis greater than or equal to 50%. Patients with 3-vessel CAD had a significantly shorter exercise duration than patients with less than 50%-diameter narrowing (5.5 +/- 2.2 vs 8.3 +/- 3.3 minutes, respectively), lower exercise heart rate (119 +/- 20 vs 149 +/- 22 beats/min) and systolic blood pressure (156 +/- 29 vs 166 +/- 33 mm Hg), more frequent chest pain (76 vs 20%) and more pronounced ST depression (-1.48 +/- 1.37 vs -0.33 +/- 0.72 mm). In addition, thallium defect size on exercise was greater in the patients with 2-vessel CAD (159 +/- 132 degrees) and 3-vessel CAD (255 +/- 132 degrees) than in patients with no CAD (28 +/- 319 degrees) or 1-vessel CAD (73 +/- 78 degrees), p greater than or equal to 0.05. Multiple regression analysis demonstrated that thallium defect size was the best predictor of extent of CAD, with exercise heart rate and presence of chest pain during exercise also predictive of extent of CAD.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Angiographic morphology in unstable angina pectoris.

Complex morphology occurs frequently in unstable angina; however, its relation to symptomatic presentation, timing of angiography and hospital outcome has not been investigated. Accordingly, coronary angiography was performed 5 +/- 2 days after qualifying rest pain in 101 consecutive patients presenting with acute coronary insufficiency (n = 67) or crescendo angina (n = 34). Significant coronary artery disease was defined as any greater than or equal to 50% stenosis, and complex morphology as any stenosis with irregularity, overhang or thrombus. Eight of the 67 patients presenting with acute coronary insufficiency later proved to have a myocardial infarction as the qualifying event (creatine kinase twice normal with elevation of MB fraction). There were no myocardial infarctions in the crescendo angina group. Complex morphology occurred in 61% of patients. Thrombus alone occurred in 27% of patients with unstable angina without myocardial infarction, with similar frequencies between the 2 clinical groups. In contrast, intraluminal thrombi were identified in 78% of patients with acute coronary insufficiency who later proved to have a myocardial infarction as the qualifying event. The need for urgent catheterization (less than 48 hours) prompted by recurrent symptoms was associated with the angiographic findings of intraluminal thrombus (46%) and complex morphology (83%). The presence of complex morphology and intracoronary thrombus was associated with a higher incidence of in-hospital cardiac events, i.e., revascularization, myocardial infarction and death, independent of the incidence of multivessel disease.

Angina Pectoris↗
PubMed1987

Induction and segregation of glial intermediate filament expression in the RT4 family of peripheral nervous system cell lines.

We have found glial fibrillary acidic protein (GFAP), the major component of astrocyte intermediate filaments, to be expressed in cell lines of the RT4 peripheral neurotumor family. The RT4 family is a "stem-cell-like" cell line, RT4-AC, that spontaneously undergoes differentiation in culture to three derivative cell types. This process, termed cell-type conversion, results in a segregation among the derivative cell types of parental cell phenotypes that have been described as neuronal-like or glial-like. We have identified a 50-kDa GFAP-immunoreactive cytoskeletal protein and GFAP mRNA in continuous RT4-AC and RT4-D (glial-type derivative) cell lines, but not in two presumptive neuronal-type cell lines. This result suggests that GFAP gene expression is coordinately coupled with the expression of other glial properties during cell-type conversion. In addition, the RT4-AC and RT4-D sublines were found to significantly express GFAP only at high cell densities and not during logarithmic growth and to express GFAP precociously during morphological differentiation following treatment with 1 mM N6, O2'-dibutyryladenosine 3',5'-cyclic monophosphate. These observations closely reflect reports of glial filament expression in astrocyte cultures, suggesting that a common regulatory mechanism is employed by central and peripheral nervous system glia.

Animals↗